Trial Outcomes & Findings for Safety Trial of Live Attenuated Influenza (H7N3) Vaccine (NCT NCT01511419)

Last Updated: 2019-04-22

Results Overview

From administration of any dose, immediate reaction measured as observed by study staff or reported by the subject to study staff in case of an anaphylactic reaction.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

40 participants

Primary outcome timeframe

2 hours post-administration on Days 0 and 28

Results posted on

2019-04-22

Participant Flow

Participant milestones

Participant milestones
Measure	LAIV H7N3 Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log egg infectious dose (EID) 50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol. Duration of treatment: Two doses were delivered, one on Day 0 and one on Day 28.	Placebo Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol Duration of treatment: Two doses were delivered, one on Day 0 and one on Day 28 placebo: 2 doses of placebo
Dose 1 STARTED	30	10
Dose 1 COMPLETED	30	10
Dose 1 NOT COMPLETED	0	0
Dose 2 STARTED	30	10
Dose 2 COMPLETED	29	10
Dose 2 NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	LAIV H7N3 Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log egg infectious dose (EID) 50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol. Duration of treatment: Two doses were delivered, one on Day 0 and one on Day 28.	Placebo Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol Duration of treatment: Two doses were delivered, one on Day 0 and one on Day 28 placebo: 2 doses of placebo
Dose 2 Physician Decision	1	0

Baseline Characteristics

Safety Trial of Live Attenuated Influenza (H7N3) Vaccine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LAIV H7N3 n=30 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol. Duration of treatment: Two doses were delivered, one on Day 0 and one on Day 28. LAIV H7N3: 2 doses of vaccine	Placebo n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol Duration of treatment: Two doses were delivered, one on Day 0 and one on Day 28 placebo: 2 doses of placebo	Total n=40 Participants Total of all reporting groups
Age, Continuous	30.1 years STANDARD_DEVIATION 10.3 • n=5 Participants	38.5 years STANDARD_DEVIATION 9.7 • n=7 Participants	32.2 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	4 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	6 Participants n=7 Participants	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 hours post-administration on Days 0 and 28

Population: Intent-to-treat (ITT) population

From administration of any dose, immediate reaction measured as observed by study staff or reported by the subject to study staff in case of an anaphylactic reaction.

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=30 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number of Participants With Immediate Reactions Immediate reaction	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Number of Participants With Immediate Reactions No immediate reaction	30 Participants	10 Participants	29 Participants	10 Participants	—	—

PRIMARY outcome

Timeframe: Greater than 2 hours through 7 days following any dose

Population: Intent-To-Treat (ITT) Population

From solicited local and systemic reactions

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=30 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Adverse Events Associated With Intranasal Vaccination Any local or systemic reaction	11 Participants	4 Participants	5 Participants	1 Participants	—	—
Adverse Events Associated With Intranasal Vaccination No local or systemic reaction	19 Participants	6 Participants	24 Participants	9 Participants	—	—

PRIMARY outcome

Timeframe: 7 days following any dose

Population: Total events among Intent-To-Treat (ITT) Population

Including unsolicited events and abnormal laboratory findings

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=44 adverse events Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=6 adverse events Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=90 adverse events Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=21 adverse events Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
All Other Adverse Events Unrelated	40 adverse events	6 adverse events	84 adverse events	20 adverse events	—	—
All Other Adverse Events Related	4 adverse events	0 adverse events	6 adverse events	1 adverse events	—	—

PRIMARY outcome

Timeframe: Within 4 weeks of receipt of any dose

Population: Intent-To-Treat (ITT) Population

Including abnormal laboratory findings

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=30 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Participants With Serious Adverse Events (SAEs) Any serious adverse event	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Participants With Serious Adverse Events (SAEs) No serious adverse event	30 Participants	10 Participants	29 Participants	10 Participants	—	—

SECONDARY outcome

Timeframe: 28 days (Dose 1) and 56 days (Dose 2)

Population: Per-Protocol (PP) Population

Seroconversion was defined as at least a four-fold rise after each dose from baseline or as the mean titer after each dose

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) Seroconversion	3 Participants	0 Participants	9 Participants	0 Participants	—	—
Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) No seroconversion	26 Participants	10 Participants	20 Participants	10 Participants	—	—

SECONDARY outcome

Timeframe: 28 days (Dose 1) and 56 days (Dose 2)

Population: Per-Protocol (PP) Population

Measured using microneutralization assay. Seroconversion was defined as at least a four-fold rise after each dose from baseline or as the mean titer after each dose

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects With Serum Neutralizing Antibodies Seroconversion	5 Participants	0 Participants	12 Participants	0 Participants	—	—
Number/Percentage of Subjects With Serum Neutralizing Antibodies No seroconversion	24 Participants	10 Participants	17 Participants	10 Participants	—	—

SECONDARY outcome

Timeframe: 28 days (Dose 1) and 56 days (Dose 2)

Population: Per-Protocol (PP) Population

Measured by enzyme-linked immunoassay (EIA). Seroconversion was defined as at least a four-fold rise after each dose from baseline or as the mean titer after each dose

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) Seroconversion	3 Participants	0 Participants	8 Participants	0 Participants	—	—
Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) No seroconversion	26 Participants	10 Participants	21 Participants	10 Participants	—	—

SECONDARY outcome

Timeframe: 28 days (Dose 1) and 56 days (Dose 2)

Population: Per-Protocol (PP) Population

Measured by enzyme-linked immunoassay (EIA). Seroconversion was defined as at least a four-fold rise after each dose from baseline or as the mean titer after each dose

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) Seroconversion	1 Participants	0 Participants	3 Participants	0 Participants	—	—
Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) No seroconversion	28 Participants	10 Participants	26 Participants	10 Participants	—	—

SECONDARY outcome

Timeframe: 28 days (Dose 1) and 56 days (Dose 2)

Population: Per-Protocol (PP) Population

From nasal wick specimen. Seroconversion was defined as at least a four-fold rise after each dose from baseline or as the mean titer after each dose

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects With Seroconversion for Mucosal IgA Seroconversion	12 Participants	1 Participants	12 Participants	1 Participants	—	—
Number/Percentage of Subjects With Seroconversion for Mucosal IgA No seroconversion	17 Participants	9 Participants	17 Participants	9 Participants	—	—

SECONDARY outcome

Timeframe: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Population: Per-Protocol (PP) Population

HAI test was performed by standard procedure with human red blood cells utilizing either 4 haemagglutinating units (HAU) of H7N3.

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Geometric Mean Titers (GMTs) for Serum Hemagglutination Inhibition (HAI) Antibodies (4 Haemagglutinating Units of H7N3) Day 0	2.8 titers Interval 2.5 to 3.1	3.3 titers Interval 2.3 to 4.7	—	—	—	—
Geometric Mean Titers (GMTs) for Serum Hemagglutination Inhibition (HAI) Antibodies (4 Haemagglutinating Units of H7N3) Day 28	3.5 titers Interval 2.8 to 4.4	3.3 titers Interval 2.3 to 4.7	—	—	—	—
Geometric Mean Titers (GMTs) for Serum Hemagglutination Inhibition (HAI) Antibodies (4 Haemagglutinating Units of H7N3) Day 56	4.7 titers Interval 3.5 to 6.1	3.5 titers Interval 2.5 to 5.0	—	—	—	—

SECONDARY outcome

Timeframe: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Population: Per-Protocol (PP) population

HAI test was performed by standard procedure with human red blood cells utilizing 2 haemagglutinating units (HAU) of H7N3.

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Geometric Mean Titers (GMTs) for Serum Hemagglutination Inhibition (HAI) Antibodies (2 Haemagglutinating Units of H7N3) Day 0	3.0 titer Interval 2.6 to 3.5	4.1 titer Interval 2.7 to 6.1	—	—	—	—
Geometric Mean Titers (GMTs) for Serum Hemagglutination Inhibition (HAI) Antibodies (2 Haemagglutinating Units of H7N3) Day 28	5.5 titer Interval 4.2 to 7.2	4.1 titer Interval 2.7 to 6.1	—	—	—	—
Geometric Mean Titers (GMTs) for Serum Hemagglutination Inhibition (HAI) Antibodies (2 Haemagglutinating Units of H7N3) Day 56	7 titer Interval 5.2 to 9.4	4.7 titer Interval 2.8 to 7.6	—	—	—	—

SECONDARY outcome

Timeframe: 0 days, 28 days (Dose 1) and 56 days (Dose 2)

Population: Per-Protocol (PP) population

Measured by microneutralization assay

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Geometric Mean Titers (GMTs) for Serum Neutralizing Antibodies Day 0	4.2 titer Interval 3.5 to 5.1	4.4 titer Interval 2.8 to 6.9	—	—	—	—
Geometric Mean Titers (GMTs) for Serum Neutralizing Antibodies Day 28	6.2 titer Interval 4.5 to 8.5	4.4 titer Interval 2.8 to 6.9	—	—	—	—
Geometric Mean Titers (GMTs) for Serum Neutralizing Antibodies Day 56	12.4 titer Interval 8.2 to 18.7	5.0 titer Interval 3.1 to 8.0	—	—	—	—

SECONDARY outcome

Timeframe: Days 1, 2, 3 & 4

Population: Intent-To-Treat (ITT) Population

Detected by real-time reverse transcriptase polymerase chain reaction (rRTPCR) in nasal swabs or conjunctival swabs or by isolation in chicken embryos.

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=30 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=30 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=30 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=30 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Vaccinated Subjects Shedding Virus After First Dose Shedding	18 Participants	3 Participants	1 Participants	0 Participants	—	—
Number/Percentage of Vaccinated Subjects Shedding Virus After First Dose No shedding	12 Participants	27 Participants	29 Participants	30 Participants	—	—

SECONDARY outcome

Timeframe: Day 29, 30, 31 and 32

Population: Per-Protocol (PP) Population

Detected by real-time reverse transcriptase polymerase chain reaction (rRTPCR) in nasal swabs or conjunctival swabs or by isolation in chicken embryos.

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=29 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=29 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects Shedding Virus After Second Dose Shedding	14 Participants	2 Participants	1 Participants	0 Participants	—	—
Number/Percentage of Subjects Shedding Virus After Second Dose No shedding	15 Participants	27 Participants	28 Participants	29 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 0, 28 & 56

Population: Per-Protocol (PP) population that received 2 doses of either vaccine or placebo

H7N3-specific T cell responses were examined in peripheral blood mononuclear cells (PBMCs) obtained from all the study subjects before vaccination (Day 0), 28 days after the first vaccination (Day 28) and 28 days after revaccination (Day 56). To calculate the frequency of virus-specific T cells we quantified all cells positive for IFNγ after in vitro stimulation with whole H7N3 virion. Increases in the antigen-specific CD4+T-cell levels exceeding 3 standard deviations from the levels in the mean of the placebo were considered positive responses.

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses Positive response	2 Participants	0 Participants	3 Participants	0 Participants	4 Participants	0 Participants
Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses No response	27 Participants	10 Participants	26 Participants	10 Participants	25 Participants	10 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 0, 28 & 56

Population: Per-Protocol (PP) population that received 2 doses of either vaccine or placebo

H7N3-specific T cell responses were examined in PBMCs obtained from all the study subjects before vaccination (Day 0), 28 days after the first vaccination (Day 28) and 28 days after revaccination (Day 56). To calculate the frequency of virus-specific T cells we quantified all cells positive for IFNγ after in vitro stimulation with whole H7N3 virion. Increases in the antigen-specific CD4+T-cell levels exceeding 3 standard deviations from the levels in the mean of the placebo were considered positive responses.

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses Positive response	5 Participants	0 Participants	6 Participants	0 Participants	7 Participants	0 Participants
Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses No response	24 Participants	10 Participants	23 Participants	10 Participants	22 Participants	10 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 0, 28 & 56

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses Positive response	1 Participants	0 Participants	3 Participants	0 Participants	3 Participants	0 Participants
Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses No response	28 Participants	10 Participants	26 Participants	10 Participants	26 Participants	10 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 0, 28 & 56

Population: Per-Protocol (PP) population that received 2 doses of either vaccine or placebo

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses Positive response	0 Participants	0 Participants	5 Participants	0 Participants	5 Participants	0 Participants
Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses No response	29 Participants	10 Participants	24 Participants	10 Participants	24 Participants	10 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 0, 28 & 56

Population: Per-Protocol (PP) population that received 2 doses of either vaccine or placebo

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses Positive response	1 Participants	0 Participants	6 Participants	0 Participants	6 Participants	0 Participants
Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses No response	28 Participants	10 Participants	23 Participants	10 Participants	23 Participants	10 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 0, 28 & 56

Population: Per-Protocol (PP) population that received 2 doses of either vaccine or placebo

Outcome measures

Outcome measures
Measure	LAIV H7N3: Dose 1 (Day 0) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 (Day 0) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 (Day 28) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 (Day 28) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Day 56 (28 Days Past Dose 2) n=29 Participants Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Day 56 (28 Days Past Dose 2) n=10 Participants Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses No response	29 Participants	10 Participants	24 Participants	10 Participants	24 Participants	10 Participants
Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses Positive response	0 Participants	0 Participants	5 Participants	0 Participants	5 Participants	0 Participants

Adverse Events

LAIV H7N3: Dose 1

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo: Dose 1

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

LAIV H7N3: Dose 2

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo: Dose 2

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Jorge Flores

PATH

Phone: (202) 822-0033

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	LAIV H7N3: Dose 1 n=30 participants at risk Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 1 n=10 participants at risk Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol	LAIV H7N3: Dose 2 n=30 participants at risk Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs. Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine. Dose: ≥7.5 log EID50/0.5 ml dose; 0.25 ml/nare. Route of administration: Intranasal aerosol.	Placebo: Dose 2 n=10 participants at risk Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine. Dose: 0.5 ml; 0.25 ml/nare Route of administration: Intranasal aerosol
Blood and lymphatic system disorders Lymphocytosis	6.7% 2/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Blood and lymphatic system disorders Monocytosis	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Blood and lymphatic system disorders Neutropenia	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Blood alkaline phosphatase decreased	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	20.0% 2/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Blood alkaline phosphatase increased	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Blood bicarbonate increased	30.0% 9/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	30.0% 3/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	16.7% 5/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	30.0% 3/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Blood bilirubin increased	16.7% 5/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	6.7% 2/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Blood calcium increased	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 3/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Number of events 1 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Blood chloride increased	6.7% 2/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 3/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Blood creatinine increased	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	20.0% 6/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Eosinophil count increased	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Hemoglobin increased	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	13.3% 4/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Lymphocyte count decreased	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	6.7% 2/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Lymphocyte count increased	20.0% 6/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	20.0% 6/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Mean cell hemoglobin concentration increased	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Monocyte count increased	16.7% 5/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	16.7% 5/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	30.0% 3/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Neutrophil count decreased	13.3% 4/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	16.7% 5/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations White blood cell count increased	6.7% 2/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	6.7% 2/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Renal and urinary disorders Leukocyturia	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Infections and infestations Nasopharyngitis	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Infections and infestations Respiratory tract infection viral	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Alanine aminotransferase increased	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	6.7% 2/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Aspartate aminotransferase increased	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Number of events 1 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Number of events 1 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Blood glucose increased	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	16.7% 5/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	20.0% 2/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Hemoglobin decreased	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Platelet count increased	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Total protein decreased	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Red blood cell increased	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Red blood cell sedimentation rate increased	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	6.7% 2/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	10.0% 1/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.
Investigations Urine leukocyte esterase positive	0.00% 0/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	3.3% 1/30 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.	0.00% 0/10 • Up to 56 days following dosing For the assessment of safety, subjects were assessed for adverse reactions twice daily (early morning and late afternoon) for 7 days. An ear, nose, and throat (ENT) examination was performed on Days 7, 28, 35, and 56. Blood and urine specimens were also collected on Days 7, 28 (prior to administration of the second dose of study vaccine or placebo), 35 and 56, for testing by routine biochemical and hematological blood tests and by urinalysis by dipstick.